Silver containing wound dressing

ABSTRACT

A wound dressing having anti-microbial activity comprises a first fibre capable of bonding with silver (1) cations. The wound dressing comprises a blend of the first fibre to which silver (1) cations are bonded and a second fibre which is substantially free from silver. The wound dressing comprises from 0.01 to 5.0 percent by weight of silver (1) cations, based on the weight of fibre.

CROSS REFERENCES

This application is a continuation of U.S. application Ser. No.15/162,890, filed May 24, 2016, which is a continuation of U.S.application Ser. No. 14/696,216 filed Apr. 24, 2015, now U.S. Pat. No.9,345,805, which is a continuation of U.S. application Ser. No.14/280,512, filed May 16, 2014, now U.S. Pat. No. 9,066,989, which is acontinuation of U.S. application Ser. No. 13/767,656, filed Feb. 14,2013, now U.S. Pat. No. 8,728,513, which is a continuation of U.S.application Ser. No. 10/311,674, filed Dec. 18, 2002, which is a U.S.National Stage application of International Application No.PCT/GB01/04204, filed Sep. 21, 2001, which claims the benefit of GB0023155.5, filed Sep. 21, 2000.

This invention relates to a wound dressing, in particular to a wounddressing having antimicrobial activity.

International Patent Applications WO 93/12275, WO 94/16746 andPCT/GB99/02093 disclose the carboxymethylation of lyocell fibre and theuse of such carboxymethylated fibre in wound dressings.

European Patent Application No. 707,793 discloses a silver-containingantimicrobial agent which comprises carboxymethylcellulose containingsilver in an amount of 0.02 to 1 percent by weight and having a degreeof substitution of at least 0.4.

Japanese Published Unexamined Patent Application 11-001,895 discloses ahygienic product such as a disposable diaper, sanitary napkin orincontinence pad which comprises water-insoluble carboxymethylcellulose(derived from woodpulp) containing 0.32% by weight silver ions.

The silver-containing fibre used in the prior art dressings discolour(turn dark brown or black) on exposure to light. In consequence, suchdressings may exhibit an unsightly appearance. Attempts have been madeto overcome this problem and are described for example in InternationalPatent Application WO 00/90173.

It is an object of the present invention to provide a wound dressing inwhich the above disadvantages are reduced or substantially obviated.

The present invention provides a wound dressing having anti-microbialactivity, which comprises a first fibre capable of bonding with silver(1) cations, characterised in that the wound dressing comprises a blendof the first fibre to which silver (1) cations are bonded and a secondfibre which is substantially free from silver.

The wound dressing according to the invention preferably comprises from0.01 to 5%, more preferably from 0.1 to 4%, even more preferably from0.25 to 3% by weight of silver (1) cations, based on the weight offibre. Most preferably, the wound dressing contains 1 to 2% by weightbased on fibre, of silver (1) cations, where the fibre is carboxymethylcellulose fibre and 0.25% to 0.75% silver (1) cations, where the fibreis an alginate fibre by weight based on the weight of fibre, of silver(1) cations.

The first fibre is preferably substantially insoluble in water andpreferably comprises a sodium carboxymethylcellulose fibre, an alginatefibre, a chitosan or chitosan derivative fibre or an acrylic fibre.Where the fibre is a carboxymethylcellulose fibre, it preferably has adegree of substitution between 0.1 and 0.4. Where the fibre is anacrylic fibre, it is preferably an acrylic fibre which incorporates acomonomer such as itaconic acid or 2-acrylamido methyl propane sulphonicacid to provide dye-sites in the fibre.

Where the fibre is an alginate fibre, it may be a calcium alginate fibreor a mixed metal alginate fibre such as a calcium/sodium alginate fibre.The alginate polymer may be one with a high mannuoronate or a highguluronate.

Wound dressings in which the first fibre is a carboxymethylcellulosefibre are particularly preferred. The second fibre may be similar ordifferent to the first fibre. Similar fibres are preferably used. Thesecond fibre should be such as not to discolour to an objectionabledegree in light, and as such should, for example, contain no silver orsuch low levels of silver that it does not discolour at all ordiscolours only to a degree which is not objectionable aesthetically.

The ratio of the first silver-containing fibre to the second fibre ispreferably in the range from 0.5 to 25% by weight, more preferably 5 to20% by weight, of the total weight of the fibre.

In order to achieve the desired overall concentration of silver ions,the first fibre preferably includes about 10% by weight, based on theweight of fibre, of silver (1) cations and is blended with a largeproportion of unsilvered fibre so as to give a blended productcontaining the desired weight of silver. The silver ions are preferablychemically bonded to the first fibre.

As specified above, the degree of substitution (D.S.) of the sodiumcarboxymethylcellulose (CMC) is preferably at least 0.1, and ispreferably less than 0.4. Such CMC is inherently insoluble in water andalso in saline solution. A higher D.S. gives at least partial solubilityin water, which is undesirable in the field to which the inventionrelates. The D.S. is more preferably in the range from 0.20 to 0.35, forexample about 0.3.

The silver ions are preferably introduced into the first CMC fibre byion-exchange, for example by contacting CMC with an aqueous solution ofa salt such as, silver(I) nitrate. As CMC often contains sodium chlorideas a by product of the reaction between cellulose and chloroacetic acidand as silver chloride is highly insoluble. It may be preferred toperform the ion-exchange reaction on a salt free grade of CMC. It ispreferred that the balance of the carboxyl groups in the CMC beneutralised with sodium ions.

The CMC is preferably derived from lyocell, as disclosed for example inWO 93/12275, WO 94/16746 and PCT/GB99/02093.

The fibrous CMC is preferably in the form of staple fibre or continuousfilament yarn. It is preferably contained within a textile article suchas a woven, knitted or most preferably a nonwoven fabric, such as aneedlepunched nonwoven fabric.

The dressings of the invention are preferably gel-forming, which makesthem advantageously low-adherent to wounds and consequently easy toremove. They are soft, conformable and absorbent. Silver metal ions arereleased slowly over an extended period of time from a wetted dressingof the invention.

The second fibre which does not contain silver is preferably also CMC,but other kinds of gel-forming fibre or of textile fibre may also beutilised. If the dressings are blended from unexposed fibre, on exposureto light, such dressings develop either a speckled appearance or a lightbrown or light grey colour which is not unsightly. However, it ispreferred to pre-expose the silver-containing fibre to light beforeblending, so that after blending the dressing is light stable and theuniformity of blending can be checked visually.

The wound dressings of the invention may contain other medicaments ifdesired.

The wound dressings of the invention are useful in the treatment ofinfected wounds, and as a prophylactic measure against infection ofuninfected wounds, also for the reduction or elimination of unpleasantodours produced by wounds.

The invention is illustrated by the following Examples, in which partsand proportions are by weight unless otherwise specified.

EXAMPLE 1 Manufacture of Master Batch Material

The optimum conditions for manufacture of a master batch material weredetermined as follows:

Sodium carboxy methyl cellulose fibre (CMC), Hydrocel®, available fromAcordis Speciality Fibres Limited of Coventry England, was soaked insilver nitrate (AgNO₃) solution in 50 volume % industrial methylatedspirit/50 volume % water and the following table shows the percentagesilver take-up after soaking, as measured by x-ray fluorescence.

% AgNO₃ Conditions 4% AgNO₃ 8% AgNO₃ 15 minutes @ 65° C. 8.1 6.1 15minutes @ ambient 12.6 11.2 4 hours @ ambient 8.0 9.0

From the above results, it was determined that higher concentrations ofsilver nitrate did not appear to be beneficial and that the use of asolution having a concentration of approximately 4% silver nitrate toproduce a fibre having a silver content of 8% would give the optimumresults. It was therefore decided to produce the master batch materialusing such a solution.

CMC tow or staple (50 g) was added to a solution of 4% silver nitrate(300 g) in industrial methylated spirit/water 50/50 at ambienttemperature. The solution was held for convenience in a round screw topbottle so that it could be rolled on a laboratory bottle roller. Thebottle was rolled for 15 minutes whereupon an ion exchange mechanismtook place which produced silver containing CMC—referred to herein assilver CMC (8% w/w, Ag).

The spent silver nitrate solution was discarded and replaced with 50/50industrial methylated spirit/water wash liquor (300 g) followed byshaking for five minutes. This washing process was repeated and finallya soft finish was used. This consisted of 0.5% polysorbate 20 (Tween) 20in 90:10 industrial methylated spirit/water (i.e. 1.5 g in 300 g).

Excess liquor was squeezed out of the fibre, which was then allowed todry at ambient temperature. The silver CMC tow was then opened out andspread onto an open bench to allow maximum access to light. Thediscolouring tow was handled periodically to expose new surfaces to thelight. This was continued until the majority of the tow assumed achocolate brown coloration (about two weeks).

The predominantly brown silver CMC tow produced was blended withuntreated carboxymethyl cellulose (CMC) fibre at the ratios shown asfollows to produce blends having 0.5%, 1.0% and 2.0% silver:

-   -   6.25% silver CMC+93.75% CMC fibre=0.5% Ag    -   12.5% silver CMC+87.50% CMC fibre=1.0% Ag    -   25.0% silver CMC+75.00% CMC fibre=2.0% Ag

Blending was accomplished by carrying out a carding operation twice toachieve a uniform blend, on hand pre-mixed fibre. The carded web wasthen cross-folded to give the desired basis weight. The web was thenbonded on a needle loom to give a coherent web from which individualdressings were cut. In addition, a conventional carboxymethyl cellulosefibre control sample was manufactured by the same method.

Absorbency Results

The master batch material was produced by the soaking of CMC fibre towin silver nitrate and the absorbency tests were first of all carried outon tow using a free swell test. It was found that the CMC fibre controlhad an absorbency of 28 g/g and the silver CMC had an absorbency of 30g/g. These differences were not considered to be significant.

Absorbency tests were then carried out on fabric produced by needlefelting from fibres as above.

Fabric absorbencies as measured by the test identified in the BritishPharmacopeia 1993 Addendum 1995 page 1706, Alginate Dressing Absorbencywere found to be as shown in the following table, in which gsm=grams persquare metre and is a measure of the amount of fabric produced.

gsm Absorbency g/g Absorbency g/piece CMC control 111 16.0 18.0 0.5%silver CMC 99 20.0 19.5 1.0% silver CMC 91 20.5 18.7 2.0% silver CMC 6522.3 14.5

As can be seen from the above table, the addition of silver was found tohave very little effect on the absorbency, if anything increasing theabsorbency on a gram per gram basis, though having less effect onabsorbency on a gram per piece basis.

After wetting for 30 minutes in saline, the fabrics which were initiallya fairly dark fawn, changed colour and became lighter and moretranslucent as time passed.

It appeared that there was no difference in the gelling propertiesbetween the CMC and the silver CMC, which is an important observation inthat the silver addition does not destroy the valuable gellingproperties.

Microbial Activity

To measure the efficiency of the silver containing material in reducingmicrobial activity, 250 g of milk was mixed with 0.2 g of fibre. Theresults were as follows:

Control (milk alone) Malodour in 2 days Control (CMC in milk) Malodourin 2 days 0.5% Silver (web) Malodour in 2 weeks 8.0% Silver (tow) NoMalodour in 3 weeks

These tests were repeated with 0.9 wt. sodium chloride additions (chosento be equivalent to the salt level in body fluids) to the milk, and thesame results were obtained. This shows that the chloride ions in thesalt were not detrimental to the antimicrobial properties of the silverin the silver CMC.

As can be seen from the above results, milk alone and milk containingCMC fibre alone went off in two days, as could be easily determined bythe smell. By comparison, where the web contained 0.5% silver, there wasa two week period before the milk went off and could be smelt. Withunblended tow containing 8% silver, no smell could be detected after athree week period when the test was stopped.

In practice, the wound treatment products utilising the invention areunlikely to be left on a wound for more than a few days, and certainlyno more than a week, so that it be seen that a blend containing 0.5%silver retains its efficiency in terms of antimicrobial effect for atleast twice the period that would be required in practice.

EXAMPLE 2

A solution of water (33.1 g) and industrial methylated spirit (IMS)(36.0 g) was made up in a black glass bottle suitable for rolling on abottle roller. To it was added silver nitrate (30.0 g) and the latterwas stirred until it dissolved. No heat was required. To this solutionwas added 12 g of high manuronic calcium alginate tow and the whole wasrolled on a bottle roller for four hours. After this period of time thetow was removed and washed in a solution (70 g) containing IMS and wateras a 50/50 mixture. Soft finish in the form of polysorbate 20 (0.7 g)was dissolved in (70 g) solution of IMS/water as a 95/5 mixture and thetow was soaked in this medium for approximately 50 minutes. The silveralginate master batch was then dried in a fume cupboard to give aproduct having 13.7% of silver overall on the fibre.

5 g of the above silver alginate master batch was weighed and cut intostaple and opened by hand. 95 g of standard high manuronic calciumalginate fibre was also cut into staple and opened. The two were blendedon the in-put feed belt of a laboratory carding machine.

The diluted silver alginate fibre was then carded, cross-folded andneedled into a non-woven web. By calculation the final product wouldcontain silver at an average level of 0.6%. It had a light grey-brownflecked mottled appearance.

In a comparative example, the same level (0.68%) of silver was applieduniformly to a batch of the same calcium alginate fibre, and it was thencarded, cross-folded, and needled to form a nonwoven web. The web wasexposed to light and developed a uniform darkish brown colour, appearingmuch darker than the mottled appearance of the blended web having thesame average amount of silver present.

The invention also contemplates multiple layer dressings some or all ofwhich layers may comprise blended product incorporated silver additions.For example, a silver containing blended layer of a non-gel formingfibre, such as a silver containing acrylic fibre blended with pureacrylic fibre could be faced with a wound contact layer of a gel formingfibre. An example of the contact layer could be an alginate fibre andthe alginate layer could be blended with a silver added fibre or mayhave no silver at all, being a simple gel forming alginate fibre.

1. A wound dressing having anti-microbial activity, comprising a firstfibre which is substantially insoluble in water having silver (I)cations bonded thereto and discoloring on exposure to light, wherein thewound dressing consists of a uniform blend of the first fibre and asecond fibre of lyocell which is substantially free from silver, saidwound dressing comprising from 0.01 to 5.0 percent by weight of silver(I) cations based on the total weight of first and second fibres,whereby the discoloration of the blend on exposure to light is lessenedcompared with the discoloration on exposure to light of a batch of thefirst fibre having the same average amount of silver cations present asis present in the blend.
 2. A wound dressing according to claim 1, whichcomprises from 0.01 to 4.0 percent by weight of silver (I) cations basedon the total weight of first and second fibres.
 3. A wound dressingaccording to claim 3, which comprises from 0.25 to 3.0 percent by weightof silver (I) cations based on the total weight of first and secondfibres.
 4. A wound dressing according to claim 1, wherein the firstfibre is selected from a group consisting of a carboxymethylcellulosefibre, an alginate fibre, a chitosan fibre, a chitosan derivative fibreand an acrylic fibre.
 5. A wound dressing according to claim 4, whereinthe first fibre is a carboxymethylcellulose fibre and the wound dressingcontains from 1.0 to 2.0 percent by weight of silver (I) cations, basedon the weight of the fibre.
 6. A wound dressing according to claim 4,wherein the first fibre is an alginate fibre and the wound dressingcontains from 0.25 to 0.75 percent by weight of silver (I) cations,based on the weight of the fibre.
 7. A wound dressing according to claim4, wherein the first fibre is an acrylic fibre which incorporates acomonomer to provide dye-sites in the fibre.
 8. A wound dressingaccording to claim 1, wherein the second fibre contains no silver or lowlevels of silver such that it discolors to a degree which is notaesthetically objectionable.
 9. A wound dressing according to claim 1,wherein the second fibre contains no silver or low levels of silver suchthat it does not discolor at all.
 10. A wound dressing according toclaim 1, wherein the ratio of the first fibre to the second fibre is inthe range of from 5 to 20% by weight of the total weight of the fibre.11. A wound dressing according to claim 1, wherein the ratio of thefirst fibre to the second fibre is in the range of from 0.5 to 25% byweight of the total weight of the fibre.
 12. A wound dressing accordingto claim 1, wherein the first fibre includes at least 8% by weight,based on the weight of the fibre, of silver (I) cations.
 13. A wounddressing according to claim 12, wherein the first fibre is preparedusing at least a 4% silver nitrate solution.
 14. A wound dressingaccording to claim 1, wherein the silver ions are chemically bonded tothe first fibre.
 15. A wound dressing according to claim 1, wherein thesilver ion are introduced into the first fibre by ion-exchange.
 16. Awound dressing according to claim 1, wherein the first fibre havingsilver (I) cations bonded thereto is pre-exposed to light prior toblending with the second fiber.